Combined hepatoprotective therapy of liver diseases

The combined use of hepatoprotectors may aim to expand the spectrum of hepatotropic action or unidirectionally increase a particular pharmacological effect due to summation or potentiation (synergism). An example of the combined effects of ademetionine and silymarin is a study that showed for the first time that the combination of ademetionine and silybinin inhibits inflammation and oxidative stress through two separate signaling pathways. Both ademetionine and silymarin inhibit the accumulation of fat in the liver, which was confirmed in a pilot clinical study. In patients with metabolic‑associated steatotic liver disease, treatment with a combination of hepatoprotectors reduced the degree of liver steatosis according to ultrasound. The synergistic effect of the combination is reflected in the treatment of depression in steatotic liver disease and the agonistic effect on the farnesoid receptor in alcoholic liver disease. The effectiveness of the combination in alcoholic hepatopathies has been proven in a clinical trial. Expanding the spectrum of therapeutic action in the combination of ademetionine and silymarin is due to the fact that despite the effectiveness of both drugs in toxic, drug‑induced liver damage, there are situations when it is more appropriate to prescribe one or the other drug. For example, silymarin is effective in death cap poisoning, while ademetionine is not. Ademetionine is effective in intrahepatic cholestasis, while silymarin is not. Other properties of silymarin are also important, as they enable the combination to expand the range of effects: antifibrotic, antitumor, immunomodulatory, choleretic, antiviral, and participation in the regulation of apoptosis and hepatocyte regeneration. Long‑term treatment with both ademetionine and silymarin help to prolong the life of patients with liver cirrhosis. Thus, the combination of ademetionine and silymarin (Adenomak Plus) is pathogenetically sound, effective, and promising, based on evidence‑based research.